Angiogenesis, formation of new blood vessels, is a key process for the skin wound healing. Several growth factors and extracellular matrix and protease/protease inhibitor systems have previously been suggested to play important roles in angiogenesis. TIE2 receptor and its ligands, angiopoietins, represent a novel ligand-receptor system that has previously shown to be a critical component in angiogenesis. My long term goal is to understand the precise roles of the TIE2 receptor and angiopoietins in angiogenesis during the skin wound healing. To obtain the initial clues on the roles of this ligand-receptor system in skin wound healing, the following two specific aims are proposed: Aim #1: To determine the temporal and spatial expression patterns of the TIE2 receptor and angiopoietins during the skin wound healing processes. This will be accomplished by the in situ hybridization and immunohistochemical methods. Aim #2: To test the hypothesis that angiopoietin-l, an activating ligand for the TIE2 receptor, can facilitate the formation and maturation of the new blood vessels and thereby enhances the skin wound healing process. This will be accomplished by using the transgenic mouse model in which angiopoietin- 1 is specifically overexpressed in proliferating epithelial cells of the basal layers of the epidermis. The blood vessel formation and maturation as well as the time course of the healing of the skin wounds produced in this transgenic mouse model will be studied. These studies are expected to contribute to our further understanding of the molecular basis of the skin wound healing. Furthermore, TIE2- angiopoietin system may eventually prove to be a novel target for developing an effective therapeutics for skin wound healing.